The hunt for a new Ebola vaccine: two scientists explain the challenges

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The ongoing Ebola virus outbreak in the Democratic Republic of Congo (DRC) and Uganda has now killed 61 people, with 359 confirmed cases. The Bundibugyo strain of the virus has a fatality rate of between 30% and 50%, and there is currently no vaccine approved for it. Two scientists at the University of Oxford, Teresa Lambe and Rebecca Makinson, are part of the group who are working to develop one. In early June, Oxford was one of three organisations to receive funding from the Coalition for Epidemic Preparedness Innovations for this work. They spoke to The Conversation Weekly podcast about what it takes to make an Ebola vaccine. This is an edited version of that conversation.

How dangerous is this moment?

Rebecca Makinson: It's feeling pretty dangerous at the moment. We're behind on the outbreak response compared to where we've been in previous outbreaks. Initial testing on this outbreak was done on a different species of virus. So we missed that key initial moment where we identified the virus that's causing the disease, and we didn't know it was Bundibugyo until later.

Cases are much higher than we'd like. And public health measures are playing catch-up.

What do we know about the Bundibugyo virus strain?

Ebola is a group of viruses – we call it a genus – that has several species. Bundibugyo is just one of them. It was first identified in 2007 in an outbreak in the Bundibugyo district of western Uganda.

Ecology-wise, there's a lot we still don't know. Like other Ebola viruses, Bundibugyo is considered a zoonotic pathogen. That means it circulates in animals and occasionally spills over into humans.

The leading hypothesis we have is that certain species of fruit bats act as a natural reservoir. We think this because related Ebola viruses have been linked to bats. We've seen viral genetic material there. But there's still a lot of work to be done on Bundibugyo.

What's different about it from the Zaire strain, for example?

Rebecca: They're similar in that they're from the same group. They are filamentous or thread-like viruses. Under the microscope, they look a bit like a shepherd's crook. And all members of this group have one surface expressed protein called the glycoprotein.

But what's different is the amino acid sequence within the glycoprotein. The two viruses are only around 60% the same in this regard.

They behave similarly, similar ecology, but we're not confident that a vaccine that we generate against one strain would be able to protect against the other because of that difference in the sequence of the glycoprotein.

Have we tried using an existing vaccine against this one?

Rebecca: We've never tried in humans, which would obviously be the gold standard of data. There have been a few limited pre-clinical studies but the data's limited and it's not looking like we're getting great cross-protection here.

Why is it so hard to make a vaccine for Ebola?

Rebecca: There are two vaccines that are licensed for use against Zaire Ebola virus. And they work well. So the challenge isn't necessarily the biology of it. The main challenge is logistical and funding related.

Unlike, say, flu or COVID, the Ebola viruses affect relatively few people globally, although the outbreaks are horrific. There's just not that normal market incentive that you'd get for pharmaceutical companies. Vaccine development can be really expensive, and there's limited commercial return.

Much of the progress when we're developing vaccines depends on governments and nonprofits and international organisations like the WHO. The other Ebola viruses that have caused more outbreaks do seem to have been prioritised.

There is also a practical challenge. Outbreaks often occur in regions with limited healthcare infrastructure. Once we've got a vaccine made we need to be able to manufacture it, transport it, store it, and get it to people quickly enough to stop the transmission.

There are two vaccines licensed for the Zaire strain. How do they work?

Rebecca: They're both viral vector vaccines. We're using a non-infectious, non-dangerous virus. They gene that gives them their cell surface protein has been deleted, and we replace it with this glycoprotein that we've been talking about for Ebola virus. And you vaccinate with that.

In no way are you ever being exposed to Ebola. It's not Ebola disease-causing or disease-causing at all. But we use this viral vector to deliver the glycoprotein to our bodies, which are then able to make antibody and T-cell responses against that protein. Both of them work that way.

One requires one shot of a vaccine called Ervebo. The other requires two doses of shots called Zabdeno and Mvabea.

You've both been involved in making a vaccine against Ebola viruses. Can you tell me about history of the ChAdOx platform?

Teresa Lambe: ChAdOx is a platform that we've worked with for many years. It's a viral vectored platform. Essentially it can be thought of as a plug and play approach. In essence we have taken a chimp adenovirus and modified it so that it's non-infectious and can act as a platform vaccine technology.

What is a good efficacy for a vaccine like this for Ebola?

Teresa: A good outcome for me is a vaccine that keeps you alive. During COVID, I was asked which was the best vaccine, and my answer was generally, “Whatever vaccine you're offered in your country, put it in your arm, as it will keep you alive.” And all the vaccines did that.

Public health measures are really important too. What have we learned from previous outbreaks?

Teresa: The first thing is about the type of protective equipment that will keep you safe while you're treating patients, and making sure we have enough.

But I think a lot of social science needs to be at the forefront. I think we sometimes don't consider what is normal practice in other countries, and therefore assume we know best. We need to learn from our neighbours and the countries where these outbreaks happen so that we don't impose a certain way of working. And I think there's work to be done about honestly representing what these vaccines and therapeutics can and can't do and talking to the public to assuage concerns.

What do you mean, 'what they can and can't do'?

Teresa: For example, during COVID there was a misconception that vaccines would stop you from feeling ill. The first thing you focus on when you're making a vaccine is keeping people safe and keeping them alive. If you can lower the symptoms, that's great, but if you can't, you're still going to try and make a vaccine that will keep people alive.

So there is sometimes a misconception that a vaccine is going to stop the spread, it's going to stop transmission, and it's going to keep you healthy all the way through an infection. I think we just need to be honest around what we can and can't expect from these different types of vaccines.

What are some of the real challenges in this epidemic about where it's happening?

Teresa: Contact tracing. I don't think that's going to be easy to do. When you're doing vaccine trials in these types of areas, typically you will vaccinate the contacts.

But if you can't trace the contacts, you're not going to be able to vaccinate them. And there is a lot of vaccine scepticism. So again, I think social scientists have a big role to play in this outbreak.

Why are there more epidemics of Ebola happening in the 21st century?

Teresa: That's quite a complicated question. Global warming – not just for Ebola outbreaks, but also for other haemorrhagic fevers and zoonotic diseases. Globalisation as well. We are encroaching into habitats, where these viruses are more easily found.

We are at least able to detect them (when we put our mind to it) and develop the diagnostics more rapidly.

Rebecca: There's also a lot more mobility. That's potentially not causing an increase in the outbreaks, but it is adding extra considerations into how we manage them.

Do you think it's likely we might see more strains?

Rebecca: I wouldn't rule it out. There's a lot going on in bats that we don't know about. Scientists are doing serosurveys in bats to try and pick this information up. But I think that's a real possibility.

Teresa Lambe is an investigator based at the University of Oxford, as part of this research portfolio has received funds from DHSC and CEPI related to filovirus vaccine research. She was one of the Principal Investigators overseeing the Oxford/AstraZeneca vaccine programme and is named as an inventor on a patent application for a vaccine against SARS CoV-2.

Rebecca Makinson is an investigator based at the University of Oxford, as part of this research portfolio has received funds from DHSC and CEPI related to filovirus vaccine research. She was one of the Principal Investigators overseeing the Oxford/AstraZeneca vaccine programme and is named as an inventor on a patent application for a vaccine against SARS CoV-2.

By Teresa Lambe, Calleva Head of Vaccine Immunology, University of Oxford And

Rebecca Makinson, Postdoctoral Researcher, Oxford Vaccine Group, University of Oxford